4-Amino-1,2,4-triazin-5-ones

ABSTRACT

Novel glyoxylic acid hydrazide-2-acylhydrazones of the formula: ##STR1## in which R 1  is hydrogen or alkyl, and 
     R 2  is alkyl or optionally substituted phenyl 
     And are prepared by reacting the corresponding glyoxylic acid ester 2-acylhydrazone with hydrazine hydrate. The compounds (I) are useful in preparing herbicidally active 4-amino-1,2,4-triazine-5-one compounds.

This is a division of application Ser. No. 531,637, filed Dec. 11, 1974,now U.S. Pat. No. 3,959,372.

The present invention relates to certain new glyoxylic acidhydrazide-2-acylhydrazone compounds.

The invention provides glyoxylic acid hydrazide-2-scylhydrazones of thegeneral formula ##STR2## in which R¹ is hydrogen or alkyl, and

R² is alkyl or optionally substituted phenyl.

When R¹ or R² is alkyl, it is preferably straight-chain or branchedalkyl of from 1 to 6, especially 1 to 4, carbon atoms. Most preferablyR¹ is methyl and R² is optionally substituted phenyl. Preferred possiblesubstituents of the optionally monosubstituted or polysubstituted phenylradical R² are straight-chain or branched alkyl of from 1 to 4 carbonatoms, alkoxy, alkylthio or alkylsulphonyl each of from 1 to 4 carbonatoms, halogen (especially fluorine, chlorine or bromine), haloalkyl orhaloalkoxy each of from 2 to 5 halogen atoms and 1 or 2 carbon atoms(especially trifluoromethyl, pentafluoroethyl or trifluoromethoxy), andnitro, nitrile and/or thiocyanato.

The invention also provides a process for the production of a glyoxylicacid hydrazide-2-acylhydrazone of formula (I) in which a glyoxylic acidester 2-acylhydrazone of the general formula ##STR3## in which R isalkyl of up to 4 carbon atoms, and

R¹ and R² have the meanings given above,

Is reacted with hydrazine hydrate in the presence of a polar organicsolvent at a temperature of 0° to 50° C.

A temperature of 0° to 30° C. is preferred

1 TO 1.5 MOLS OF HYDRAZINE HYDRATE ARE NORMALLY USED PER MOL OF THECOMPOUND OF FORMULA (II).

The reaction is generally carried out under ambient pressure.

The compounds of the formula (I) may be isolated by cooling the reactionmixture to room temperature, filtering off the precipitate which hascrystallized out, rinsing it with a little ethanol and drying it.

The glyoxylic acid ester 2-acylhydrazones of the formula (II) used asstarting compounds are generally known and can be prepared according tocustomary methods as disclosed in German Offenlegungsschrift (GermanPublished Specification) No. 2,107,757. The following may be mentionedindividually as examples of the new glyoxylic acidhydrazide-2-acylhydrazones (I) which can be prepared from these by theprocess according to the invention: phenylglyoxylic acidhydrazide-2-acetylhydrazone, phenylglyoxylic acidhydrazide-2-propionylhydrazone, 4-fluorophenylglyoxylic acidhydrazide-2-propionylhydrazone, 3-methylphenylglyoxylic acidhydrazide-2-propionylhydrazone, 3-trifluoromethylphenylglyoxylic acidhydrazide-2-propionylhydrazone, 4-methoxyphenylglyoxylic acidhydrazide-2-propionylhydrazone, tertiary butylglyoxylic acidhydrazide-2-acetylhydrazone, 3-methoxyphenylglyoxylic acidhydrazide-2-acetylhydrazone, 3,4-dimethoxyphenylglyoxylic acidhydrazide-2-acetylhydrazone, 4-methylthiophenylglyoxylic acidhydrazide-2-acetylhydrazone, 4-methylsulphonylphenylglyoxylic acidhydrazide-2-propionylhydrazone, 4-chlorophenylglyoxylic acidhydrazide-2-propionylhydrazone and 4-trifluoromethoxyphenylglyoxylicacid hydrazide-2-propionylhydrazone.

Polar organic solvents can be used as diluents for the process accordingto the invention. Preferred ones include alcohols such as ethanol, n-and iso-propanol and n- and iso-butanol, acid amides such asdimethylformamide or hexamethylphosphoric acid triamide, and sulphoxidessuch as dimethylsulphoxide.

It is very surprising that the new glyoxylic acidhydrazide-2-acylhydrazones (I) of the invention are, on the one hand,stable compounds which can be isolated easily and, on the other hand, atelevated temperature undergo a smooth cyclization -- by intramolecularreaction between the N-1 of the acid hydrazide group and the keto group,the activation of which is low, of the acylhydrazone group -- withformation of 4-amino-1,2,4-triazin-5-ones which can even be"analytically pure".

The invention therefore also provides a process whereby a glyoxylic acidhydrazide-2-acylhydrazone of formula (I) is converted into a4-amino-1,2,4-triazin-5-one of the general formula ##STR4## in which R¹and R² have the meanings given above,

which comprises heating the compound of formula (I) in the presence of apolar organic solvent at a temperature of 60° to 150° C.

This heating is preferably carried out in the presence of awater-binding agent. Preferred agents include anhydrous powdered alkalimetal carbonates, for example sodium carbonate, alkali metal sulphates,for example sodium sulphate, and alkali metal acetates, for examplesodium acetate. However, the reaction can also be carried out withoutsuch an agent.

Polar organic solvents are also used as diluents for this heating step;the preferred ones are as described above.

The preferred heating temperature is 80° to 120° C. The heating is ingeneral carried out under ambient pressure.

In carrying out the heating step, 1 to 1.2 mols of water-binding agentare generally employed per mol of compound of formula (I).

The triazinones (III) may be isolated in substantially the same manneras the compounds of formula (I). A further fraction can in each case beobtained from the mother liquors by concentration. The triazinones (III)can be used direct as herbicides without further purification, sincethey can be obtained in a very pure form by the process according to theinvention.

If phenylglyoxylic acid ethyl ester 2-acetylhydrazone is used as thestarting material, the course of the two processes of the invention canbe represented by the following formula schemes. ##STR5##

The 4-amino-1,2,4-triazin-5-ones (III) which can be prepared utilizingthe inventive compounds are known as herbicides of good activity, as setforth in German Offenlegungsschriften (German Published Specifications)Nos. 2,107,757 and 2,138,031; furthermore, the use of those activecompounds of the formula (III) herein wherein R¹ is methyl and R² isoptionally substituted phenyl, as selective beet herbicides, forms thesubject of an earlier patent application published as GermanOffenlegungsschrift (German Published Specification) No. 2,224,161.

It is already disclosed that 4-amino-1,2,4-triazin-5-ones are obtainedwhen glyoxylic acid ester 2-acylhydrazones are reacted with hydrazine orhydrazine derivatives in the presence of a basic catalyst and of anorganic solvent at 50° to 150° C, in accordance with the followingformula scheme as disclosed in German Offenlegungsschrift (GermanPublished Specification) No. 2,107,757: ##STR6## in which R₁ ' is alkylor cycloalkyl,

R₄ ' is C(CH₃)₃ or C₆ H₅,

R' is alkyl, and

R₂ ' and R₃ ' are hydrogen or alkyl.

However, the yields are not always satisfactory, especially when theprocess is carried out on an industrial scale.

Furthermore, it has been disclosed that 4-amino-1,2,4-triazin-5-ones canbe obtained when diazabutadienes are reacted with hydrazine oralkylhydrazine in the presence of an acid-binding agent and in thepresence of a diluent at 0° to 150° C. in accordance with the followingformula scheme, in German Offenlegungsschrift German PublishedSpecification) No. 2,138,031: ##STR7## in which R" is chlorine oralkoxy,

R₁ " is alkyl or cycloalkyl,

R₂ " is alkyl or H, and

R₄ " is C(CH₃)₃ or C₆ H₅.

This process, again, is not easy to carry out on an industrial scale.The diazabutadiene used as the starting material frequently stillcontains phosphorus oxychloride impurities and is therefore corrosiveand of low stability. Furthermore, the purity of the triazinonesproduced is not always satisfactory so that the process has to befollowed by additional purification processes.

Furthermore, it has been disclosed that 1,2,4-triazin-5-ones areobtained when amidrazones are reacted with α-keto-acid esters in thepresence of an organic solvent at temperatures of -5° to 10° C. andthereafter heated to the boil in the presence of dimethylformamide, inaccordance with the following formula scheme (collection Czechoslov.Chem. Commun. 36 (1971) 1955-1963): ##STR8## in which R₁ "' is methyl orphenyl, and

R₄ "' is hydrogen or methyl

(But 4-amino-1,2,4-triazine-5-ones cannot be prepared in this way).

The production of 4-amino-1,2,4-triazin-5-ones using the presentinvention has a number of technical advantages over these known methods.Thus, the glyoxylic acid ester 2-acylhydrazones (II) used as startingmaterials are easily accessible. The glyoxylic acidhydrazide-2-acylhydrazones (I) which function as intermediate productsare also easily accessible by the process according to the invention andcan be isolated relatively pure, as stable substances. The herbicidallyactive 4-amino-1,2,4-triazine-5-ones can be prepared in very good yieldsand excellent purity according to the invention. Effluent problemscaused by solvents do not arise since the solvents can be recovered bydistillation and are, furthermore, non-toxic.

The following examples illustrate the invention in more detail.

EXAMPLE 1A Preparation on a Laboratory Scale of a Compound of GeneralFormula (I) ##STR9##

234 g (1 mol) of phenylglyoxylic acid ethyl ester 2-acetylhydrazones ofmelting point 88° C. were suspended in 1.5 liters of ethanol and 75 g (1mol) of hydrazine hydrate were added over the course of 20 minutes atroom temperature, while stirring. In the course thereof, the temperaturerose to about 30° C. A clear, slightly yellowish-colored solution wasproduced, from which crystals began to separate out after a short time.After stirring for 4 hours at room temperature, the precipitate whichhad been produced, was filtered off, rinsed with a little ethanol anddried.

180 g (82% of theory) of phenylglyoxylic acidhydrazide-2-acetylhydrazone of melting point 177° C. were obtained.

EXAMPLE 1B Preparation on the Laboratory Scale of a Compound of GeneralFormula (III) ##STR10## Variant (a)

175 g (0.8 mol) of phenylglyoxylic acid hydrazide-2-acetylhydrazone weredissolved in 2 liters of ethanol and the solution was heated to boilunder reflux for 12 hours. After cooling, the product which hadprecipitated was filtered off. The mother liquor was partially freedfrom the solvent; on cooling, a further precipitate was obtained, whichwas also filtered off and well washed with water. The combinedprecipitates were dried. 123 g (76% of theory) of4-amino-3-methyl-6-phenyl-1,2,4-triazin-5-(4H)-one of melting point160°-163° C. were obtained.

Variant (b)

Varient (a) was repeated except that 66 g (0.8 mol) of anhydrous sodiumacetate were added to the reactants specified. This increased the yieldto 148 g (92% of theory); the melting point did not change.

EXAMPLE 1C Preparation on an Industrial Scale of a Compound of GeneralFormula (I)

262 kg (325 liters) of isopropanol and 84 kg (359 mols) ofphenylglyoxylic acid ethyl ester 2-acetylhydrazone were initiallyintroduced into a 500 liter stirred kettle. 27 kg (540 mols) ofhydrazine hydrate were added over the course of about 30 minutes at roomtemperature. Thereafter the mixture was stirred overnight at roomtemperature.

The resulting precipitate of phenylglyoxylic acidhydrazide-2-acetylhydrazone was filtered off and used in Example 1D inthe moist state in which it was obtained from a centrifuge.

EXAMPLE 1D Preparation on an Industrial Scale of a Compound of GeneralFormula (III)

455 kg (570 liters) of n-propanol, 31.3 kg (381.7 mols) of sodiumacetate and 84 kg of phenylglyoxylic acid hydrazide-2-acetylkydrazone,in the moist state in which it had obtained from a centrifuge (Example1C), were initially introduced into a stirred kettle of 1,200 literscapacity. The kettle was brought to an internal temperature of 95°-100°C. and stirred for 20 hours at this temperature. After cooling to 5°-10°C., the resulting precipitate was filtered off, twice washed well withwater and dried at 60° C.

The mother liquor was partially freed from the solvent, water was addedto the viscous crystal sludge and the resulting precipitate was filteredoff, well rinsed with water and dried.

50 kg (69% of theory, relative to phenylglyoxylic acid ethyl ester2-acetylhydrazone) of 4-amino-3-methyl-6-phenyl-1,2,4-triazin-5-(4H)-oneof melting point 160°-163° C. were obtained.

The compound listed in Tables 1 (compounds of formula (I) and 2(compounds of formula (III)) which follow were prepared

                  Table 1                                                         ______________________________________                                        Compounds of formula (I):                                                     ______________________________________                                         ##STR11##                     (I)                                                                              Melting                                     Example No.                                                                             R.sup.1  R.sup.2        point (° C)                          ______________________________________                                        (I)-2     C.sub.2 H.sub.5                                                                         ##STR12##     149                                         (I)-3     C.sub.2 H.sub.5                                                                         ##STR13##     173                                         (I)-4     C.sub.2 H.sub.5                                                                         ##STR14##     159                                         (I)-5     C.sub.2 H.sub.5                                                                         ##STR15##     140                                         (I)-6     C.sub.2 H.sub.5                                                                         ##STR16##     175                                         (I)-7     CH.sub.3                                                                                ##STR17##     185                                         (I)-8     CH.sub.3                                                                                ##STR18##     182                                         ______________________________________                                    

                  table 2                                                         ______________________________________                                        Compounds of formula (III)                                                     ##STR19##                                                                    Example                           Melting                                     No.     R.sup.1  R.sup.2          point (° C)                          ______________________________________                                        (III)-2 C.sub.2 H.sub.5                                                                        C(CH.sub.3).sub.3                                                                              154                                         (III)-3 C.sub.2 H.sub.5                                                                         ##STR20##       164                                         (III)-4 C.sub.2 H.sub.5                                                                         ##STR21##       148                                         (III)-5 C.sub.2 H.sub.5                                                                         ##STR22##       164-166                                     (III)-6 C.sub.2 H.sub.5                                                                         ##STR23##       167-168                                     (III)-7 C.sub.2 H.sub.5                                                                         ##STR24##       156                                         (III)-8 C.sub.2 H.sub.5                                                                         ##STR25##       108                                         (III)-9 C.sub.2 H.sub.5                                                                         ##STR26##       133                                         (III)-10                                                                              C.sub.2 H.sub.5                                                                         ##STR27##       149                                         (III)-11                                                                              C.sub.2 H.sub.5                                                                         ##STR28##       133                                         (III)-12                                                                              C.sub.2 H.sub.5                                                                         ##STR29##       154                                         (III)-13                                                                              C.sub.2 H.sub.5                                                                         ##STR30##       132                                         (III)-14                                                                              C.sub.2 H.sub.5                                                                         ##STR31##       159-160                                     (III)-15                                                                              C.sub.2 H.sub.5                                                                         ##STR32##       178                                         (III)-16                                                                              C.sub.2 H.sub.5                                                                         ##STR33##       193-195                                     (III)-17                                                                              C.sub.2 H.sub.5                                                                         ##STR34##       180                                         (III)-18                                                                              C.sub.2 H.sub.5                                                                         ##STR35##       126                                         (III)-19                                                                              H        C(CH.sub.3).sub.3                                                                              113-114                                     (III)-20                                                                              CH.sub.3                                                                                ##STR36##       206                                         (III)-21                                                                              CH.sub.3 C(CH.sub.3).sub.3                                                                              158-159                                     (III)-22                                                                              CH.sub.3                                                                                ##STR37##       167-169                                     (III)-23                                                                              CH.sub.3                                                                                ##STR38##       199                                         (III)-24                                                                              CH.sub.3                                                                                ##STR39##        97                                         (III)-25                                                                              CH.sub.3                                                                                ##STR40##       107                                         (III)-26                                                                              CH.sub.3                                                                                ##STR41##       140                                         (III)-27                                                                              CH.sub.3                                                                                ##STR42##       178                                         (III)-28                                                                              CH.sub.3                                                                                ##STR43##       140                                         (III)-30                                                                              CH.sub.3                                                                                ##STR44##       169                                         (III)-31                                                                              CH.sub.3                                                                                ##STR45##       189-191                                     (III)-32                                                                              CH.sub.3                                                                                ##STR46##       209                                         (III)-33                                                                              CH.sub.3                                                                                ##STR47##       233                                         (III)-34                                                                              CH.sub.3                                                                                ##STR48##       220                                         (III)-35                                                                              CH.sub.3                                                                                ##STR49##       129                                         (III)-36                                                                              CH.sub.3                                                                                ##STR50##       163                                         (III)-37                                                                              CH.sub.3                                                                                ##STR51##       137                                         ______________________________________                                    

it will be understood that the foregoing specification and examples areillustrative but not limitative of the present invention inasmuch asother embodiments within the spirit and scope of the invention willsuggest themselves to those skilled in the art.

What is claimed is:
 1. Process for the preparation of a4-amino-1,2,4-triazin-5-one compound of the formula: ##STR52## whichprocess comprises heating a glyoxylic acid hydrazide-2-acylhydrazonecompound of the formula ##STR53## wherein R¹ is hydrogen or alkyl, andR²is alkyl, phenyl or substituted phenylin the presence of a polar organicsolvent at a temperature of 60° to 150° C.
 2. Process as claimed inclaim 1 wherein the reaction temperature is from 80° to 120° C. 3.Process as claimed in claim 2 wherein the heating is carried out in thepresence of a water binding agent.
 4. Process as claimed in claim 3wherein 1 to 1.2 moles of water binding agent are used per mole of theglyoxylic acid hydrazide-2-acylhydrazone compound.
 5. Process as claimedin claim 1 wherein said glyoxylic acid hydrazide-2 -acylhydrazonecompound is phenylglyoxylic acid hydrazide-2-acetylhydrazone.
 6. Processas claimed in claim 5 wherein said phenylglyoxylic acidhydrazide-2-acetylhydrazone is dissolved in ethanol and the solution isheated to boil for approximately 12 to 20 hours.
 7. Process as claimedin claim 6 wherein sodium acetate is added as a water-binding agent.